Heparin-coated cardiopulmonary bypass circuits selectively deplete the pattern recognition molecule ficolin-2 of the lectin complement pathway in vivo.

The complement system can be activated via the lectin pathway by the recognition molecules mannose-binding lectin (MBL) and the ficolins. Ficolin-2 exhibits binding against a broad range of ligands, including biomaterials in vitro, and low ficolin-2 levels are associated with increased risk of infections. Thus, we investigated the biocompatibility of the recognition molecules of the lectin pathway in two different types of cardiopulmonary bypass circuits. Bloods were drawn at five time-points before, during and postoperatively from 30 patients undergoing elective cardiac surgery. Patients were randomized into two groups using different coatings of cardiopulmonary bypass circuits, Phisio® (phosphorylcholine polymer coating) and Bioline® (albumin-heparin coating). Concentrations of MBL, ficolin-1, -2 and -3 and soluble C3a and terminal complement complex (TCC) in plasma samples were measured. Ficolin-3-mediated complement activation potential was evaluated with C4, C3 and TCC as output. There was no significant difference between the two circuit materials regarding MBL, ficolin-1 and -3. In the Bioline® group the ficolin-2 levels decreased significantly after initiation of surgery (P < 0.0001) and remained reduced throughout the sampling period. This was not seen for Phisio®-coated circuits. Ficolin-3-mediated complement activation potential was reduced significantly in both groups after start of operation (P < 0.0001), whereas soluble C3a and TCC in the samples were increased (P < 0.0001). Ficolin-2 was depleted from plasma during cardiac surgery when using heparin-coated bypass circuits and did not reach baseline level 24 h postoperation. These findings may have implications for the postoperative susceptibility to infections in patients undergoing extracorporeal circulation procedures.

Proliferation signal inhibitors and post-transplant malignancies in heart transplantation: practical clinical management questions.

Although malignancy is a major threat to long-term survival of heart transplant (HT) recipients, clear strategies to manage immunosuppression in these patients are lacking. Several lines of evidences support the hypothesis of an anticancer effect of proliferation signal inhibitors (PSIs: mammalian target of rapamycin [mTOR] inhibitors) in HT recipients. This property may arise from PSI's ability to replace immunosuppressive therapies that promote cancer progression, such as calcineurin inhibitors or azathioprine, and/or through their direct biological actions in preventing tumor development and progression. Given the lack of randomized studies specifically exploring these issues in the transplant setting, a collaborative group reviewed current literature and personal clinical experience to reach a consensus aimed to provide practical guidance for the clinical conduct in HT recipients with malignancy, or at high risk of malignancy, with a special focus on advice relevant to potential role of PSIs.

Biocompatibility and pathways of initial complement pathway activation with Phisio- and PMEA-coated cardiopulmonary bypass circuits during open-heart surgery.

A randomized open-heart surgery study comprising 30 patients was undertaken to compare the biocompatibility of Phisio-(phosphorylcholine) and PMEA-(poly-2-methoxyethyl acrylate) coated cardiopulmonary bypass (CPB) circuits and to assess the initial complement pathway activation during open-heart surgery. Blood samples were obtained at five time points, from the start of surgery to 24 hours postoperatively. The following analyses were performed: haemoglobin, lactate dehydrogenase, leukocyte and platelet counts, myeloperoxidase and neutrophil-activating peptide-2, thrombin-anti-thrombin complexes, syndecan-1 and the complement activation products C1rs-C1-inhibitor complexes, C4bc, C3bc, C3bBbP and the terminal complement complex (TCC). No significant inter-group difference was found in any parameters, except for the concentration of TCC which was moderately lower in the PMEA group at termination of CPB. Complement activation during open-heart surgery was mainly mediated through the alternative pathway. In conclusion, PMEA- and Phisio-coated circuits displayed similar biocompatibility with respect to inflammatory and haemostatic responses during and after open-heart surgery.

Comparable biocompatibility of Phisio- and Bioline-coated cardiopulmonary bypass circuits indicated by the inflammatory response.

BACKGROUND: The biocompatibility of cardiopulmonary bypass surfaces has been improved by heparin and polymer surface modifications. The present study compared the effect of two such coatings on the inflammatory reactions after open heart surgery. METHODS: Thirty patients undergoing elective heart surgery were randomly assigned to receive one of two types of coated circuits: Bioline (n=15) or phosphorylcholine (Phisio, n=15). The platelet and leukocyte counts, neutrophil activation (myeloperoxidase), complement activation (C3a and TCC), concentrations of lactate dehydrogenase, 27 cytokines (including interleukins, chemokines and growth factors), thrombin-antithrombin complexes, and the endothelial cell marker syndecan-1 were analyzed at five predetermined time points until 24 hrs post operatively. RESULTS: Most measurements were comparable in both groups. However, myeloperoxidase was significantly higher in the Bioline group (p < 0.001). Postoperative lactate dehydrogenase concentrations were significantly higher in the Phisio group (p<0.01) and the maximal concentration of thrombin-antithrombin complexes 2 hours postoperatively tended to be higher in the Phisio group (p=0.08), consistent with a longer aortic cross-clamp and cardiopulmonary bypass time. CONCLUSIONS: The two circuits exhibited a comparable degree of in vivo biocompatibility.

Pig endogenous retrovirus--a threat to clinical xenotransplantation?

Transplantation shows good results for patients with end-stage disease, but there is an increasing lack of organs. Xenotransplantation, the transfer of live animal cells, tissues, or organs to another species, offers a potential solution to this shortfall. Pig is regarded as the animal of choice for this purpose. Meanwhile demonstration of pig endogenous retrovirus (PERV) in all porcine herds has caused serious concern with respect to a possible transmission of the virus to humans with a transplanted organ. Transmission to human cells has been documented under certain in vitro conditions. However, no such transmission has been demonstrated in vivo. The possible consequences of introducing PERV into immunocompromised human organisms are not known and it is necessary to collect more information. Novel and sensitive genomic assays to detect PERV infection are now available in addition to established virological, immunoserological and molecular methods. In order to minimise the risk of PERV transmission rigorous procedures should be established. International guidelines to reduce the risk should be followed. Although a number of immunological, physiological and virological questions need to be answered before the introduction of xenotransplantation as an alternative clinical treatment, some problems can only be solved by judicious clinical trials.

Is atrial fibrillation caused by extracorporeal circulation?

BACKGROUND: Atrial fibrillation is the most common rhythm disturbance encountered after open heart operations, with a reported incidence up to 40%. Despite its high incidence and clinical relevance its etiology remains obscure. It has been hypothesized that atrial fibrillation might be related to extracorporeal circulation. We performed a retrospective study (January 1, 1997 to December 31, 1997) comparing the incidence of atrial fibrillation in 3 groups of patients revascularized with and without extracorporeal circulation. METHODS: The first group comprised patients with coronary artery disease operated on with standard revascularization technique with cardiopulmonary bypass (n = 685). The second group included patients who had minimally invasive coronary artery bypass grafting without the use of extracorporeal circulation (n = 19). Patients in the third group had off-pump transmyocardial laser revascularization (n = 19). RESULTS: There was no significant difference in the incidence of atrial fibrillation in the group that had conventional coronary artery bypass and the group that had minimally invasive coronary artery bypass without cardiopulmonary bypass. The incidence of atrial fibrillation was significantly lower in the transmyocardial laser group compared with the other two groups. CONCLUSIONS: The present study found that postoperative atrial fibrillation is not caused solely by extracorporeal circulation, but patients who had transmyocardial laser revascularization had a significantly lower incidence of atrial fibrillation.

C1-inhibitor attenuates hyperacute rejection and inhibits complement, leukocyte and platelet activation in an ex vivo pig-to-human perfusion model.

Xenotransplantation may be a future alternative due to increased shortage of organs. Classical complement activation is central in hyperacute rejection in pig-to-human combinations. We investigated the effects of C1-inhibitor (C1-INH), a regulator of the complement and contact systems, on hyperacute rejection. Pig kidneys were perfused with fresh human blood to which either C1-INH (n = 6) or human serum albumin (n = 6) was added. The survival of the C1-INH perfused kidneys (mean 327 min) was significantly longer (p < 0.00001) than the controls (79 min). C1-INH substantially inhibited complement activation (C1rs-C1-INH complexes, C4bc, C3bc and terminal complement complex) (p < 0.001 for all) compared with the marked complement activation in the controls. No contact activation was found. Leukocytes and platelets were substantially activated (counts, myeloperoxidase, beta-thromboglobulin, thrombospondin, soluble P-selectin) in the control group, and this activation was markedly reduced by C1-INH (p < 0.02 for all). Immunohistochemistry showed less C1q, C3, TCC, IgG and fibrin deposition in the C1-INH group. C1-INH may be useful to attenuate hyperacute rejection, probably through inhibition of complement. The reduced activation of neutrophils and platelets may mainly be secondary to inhibition of complement.

Monocusp valve in right ventricular outflow tract.

Sixty patients aged 5 days-10.3 years (mean 2.9 years) received monocusp valve implants in the right ventricular outflow tract in corrective surgery for congenital heart disease. The free edge of the monocusp valve was attached to the posterior wall of the new pulmonary tract to cover the entire root of the pulmonary tract when the monocusp valve closed. Follow-up was 3.8 (0-11.5) years. Early mortality was 8.3% (5/60) and late mortality 3.6% (2/55). Monocusp valve regurgitation developed in all patients. Moderate or severe valve failure was found in 30 patients at median 1.4, mean 2.2 (0.2-6.8) years postoperatively. Repeat surgery was performed in seven cases because of monocusp failure. It is emphasized that monocusps potentially give short-term reduction of pulmonary regurgitation when used for right ventricular outflow tract reconstruction. Only long-term follow-up can disclose whether all patients with a monocusp valve will require repeat surgery.

Up to eight years' follow-up of 997 patients receiving the CarboMedics prosthetic heart valve.

BACKGROUND: The aim of the study was to evaluate our clinical experience with the CarboMedics Heart Valve Prosthesis. METHODS: Nine hundred ninety-seven consecutive patients underwent mechanical valve implantation (aortic, 771; mitral, 169; double, 52; tricuspid, 5) with this prosthesis from September 1987 through December 1993. The mean age was 62.3+/-13.7 years (range, 0.4 to 84 years); 56.6% (564 patients) were men. Four hundred seventy patients (47.1%) underwent additional surgical procedures. Mean follow-up was 4.1+/-2.2 years (range, 0 to 8.3 years) with a total of 4,040 patient-years. RESULTS: Early mortality was 5.0% (50/997; aortic, 4.4%; mitral, 6.4%; double, 9.6%). Late mortality was 14.8% (140/947). Survival at 7 years was 75.9%+/-1.8% (aortic, 78.4%+/-2%; mitral, 70.7%+/-4.5%; double, 60.8%+/-7.4%). When matched for sex and age and compared with the normal Norwegian population, our patients had an increased standard mortality ratio in both men (1.9+/-0.4) and women (2.9+/-0.6). The linearized rate of major thromboembolism was 0.9% per patient-year, valve thrombosis 0.2% per patient-year, major bleeding event 0.6% per patient-year, paravalvular leak needing reoperation 0.5% per patient-year, prosthetic valve endocarditis 0.1% per patient-year, and of all reoperations 0.6% per patient-year. CONCLUSIONS: The CarboMedics Heart Valve Prosthesis has incidences of morbid events comparable with or better than reported for other mechanical valves.

Carpentier-Edwards bioprosthesis. Experiences of 17 years with analysis of risk factors of early mortality.

Isolated aortic (AVR, N = 71), mitral (MVR, N = 103), tricuspid (TVR, N = 3), pulmonary (PVR, N = 8), combined AVR + MVR (N = 4), or combined MVR + TVR (N = 2) valve replacement with a Carpentier-Edwards porcine bioprosthesis was performed in 191 patients between 1979 and 1986. Mean age was 56.9 +/- 17 (range 5-80) years in the total cohort. The operative mortality rates were 5.6% and 8.7%, respectively, for AVR and MVR. Mean observation time was 8 +/- 4.2 (0-16.7) years (total = 1.467 patient-years). Follow-up was 100% complete with respect to mortality. There were 78 late deaths (44%). Actuarial survival rates at 5 and 10 years were 73.2 +/- 5.2 and 52.1 +/- 6.6 for AVR and 76.7 +/- 4.2 and 61.6 +/- 4.8 for MVR. Coronary artery disease, concomitant coronary artery bypass grafting and emergency operation were significant risk factors of early mortality (p < 0.05). Postoperatively, sepsis and multiorgan failure were associated with early mortality (p < 0.05). The 10-year actuarial freedom from structural deterioration for AVR was 89 +/- 4.6 and 76.4 +/- 4.3 for MVR. It is concluded that structural valve failure is the most important factor that adversely affects the performance of Carpentier-Edwards bioprosthesis.

Homografts for right ventricular outflow tract reconstruction in congenital heart disease.

In 49 patients aged 2.2-34.8 (mean 11) years, homografts (20 aortic, 29 pulmonary) were implanted in the right ventricular outflow tract as an isolated procedure or part of corrective surgery for congenital heart disease: tetralogy of Fallot with pulmonary stenosis (23 cases), pulmonary atresia with ventricular septal defect (10 cases) truncus arteriosus (8 cases) or transposition of the great arteries with pulmonary stenosis (8 cases). Previous palliative procedures had been performed on 34 patients, and 37 had undergone repair of right ventricular outflow tract, with one to four sternotomies prior to homograft implantation. Homograft valve sizes ranged from 14 to 25 mm internal diameter. Concomitant intra- or extracardiac procedures were performed in 29 cases. Follow-up was complete at a mean of 3 +/- 0.3 (0-8) years. Early and total mortality was 2.0% (1/49), due to sepsis and multi-organ failure unrelated to the homograft. At follow-up all but one of the patients had an improved New York Heart Association function class. Eight patients (16.3%) with a mean age of 9.2 +/- 1.8 (2.8-15.5) years at implantation had homograft malfunction (stenosis in three, regurgitation in two and combined in three) at follow-up, averaging 4.1 +/- 1.0 (0.4-6.9) years, with no significant difference between aorta and pulmonary homograft subsets. Freedom from structural valve deterioration was 46.6 +/- 22% for pulmonary and 32.3 +/- 21.3% for aortic homografts at the 7-year follow-up (difference not significant). In two patients an aortic homograft was uneventfully replaced. In conclusion, homograft implantation in patients with right ventricular outflow tract obstruction improves function class and can entail low mortality and morbidity, even after multiple previous median sternotomies.

[Aortic coarctation and complex heart disease. Surgical treatment during the first year of life]. / Koarktasjon av aorta og kompleks hjertelidelse. Kirurgisk behandling i første leveår.

During the five years 1990 through 1994, 70 neonates and infants had surgery for coarctation of the aorta. 30 patients with complex coarctation of the aorta underwent a first stage correction with supplementary ductus ligation and pulmonary artery banding as needed. The mode of surgical repair of coarctation was end-to-end anastomosis in ten patients and patch graft in 20 patient. Mean follow-up was 766 (range 3-1812) days. Mortality after primary procedure was 16.6% (5/30) and after secondary procedure 11.1% (2/18). Three surviving patient developed recoarctation, but only one patients needed re-operation. In spite of improvement in neonatal cardiac surgery, we conclude that a staged approach is still the current treatment in most cases of complex coarctation of the aorta.

The CarboMedics valve: midterm follow-up with analysis of risk factors.

BACKGROUND: This study examined the midterm results with the CarboMedics prosthetic valve. METHODS: From 1987 through 1991 a total of 569 patients received the CarboMedics prosthesis. RESULTS: Early mortality was 4.9% and related to emergency operation, presence of diabetes mellitus, coronary artery disease, preoperative New York Heart Association class, duration of cardiopulmonary bypass, and aortic cross-clamp time. Midterm follow-up with respect to mortality was 100% complete. All patients were followed up in the hospital after 1 year. In addition 86% of the patients responded to a questionnaire. Mean follow-up was 3 years (range, 0 to 5.6 years). Cumulative survival at 1 and 4 years was 91.2% +/- 1.2% and 83.7% +/- 1.8%, respectively. Five patients experienced obstructive valve thrombosis (0.3%/patient-year), 16 patients had major thromboembolic events (0.9%/patient-year), and 10 patients had major warfarin-related bleeding (0.6%/patient-year) requiring hospitalization or blood transfusions. Eight patients were reoperated on for paraprosthetic leak (0.4%/patient-year). Prosthetic valve endocarditis developed in 4 patients (0.2%/patient-year). No structural valve failure was observed. CONCLUSIONS: Midterm follow-up demonstrates that the CarboMedics mechanical prosthesis is reliable and has an acceptable rate of valve-related complications.

Congenital pulmonary arteriovenous fistula.

Pulmonary arteriovenous fistula wherein the malformation has venous drainage directly to the left atrium is a rare anomaly. Two case reports present such unusual arteriovenous malformations successfully treated by surgery.

CarboMedics valve in congenital heart disease. Midterm follow-up study of 14 patients.

In 14 patients aged 5-329 (mean 131) months a CarboMedics valve was implanted because of congenital heart disease. The preoperative NYHA function class was III-IV in ten cases. Seven aortic and seven atrioventricular valves were replaced without early mortality. All patients were followed up, with mean observation time 27 months (total 384 months). One of the 14 patients died of heart failure 10 months postoperatively. Thrombosis occurred in four valves, three in tricuspid and one in mitral position. In all patients who received only warfarin, anticoagulation was demonstrably inadequate. Consequently we now recommend antiplatelet medication in addition to warfarin for children with atrioventricular mechanical valve replacement. In our experience the complication rate with CarboMedics prosthesis is acceptable, provided that anticoagulant therapy is adequate.

[Surgical treatment of lumbar disk prolapse. A 20-year material]. / Operativ behandling av lumbalt skiveprolaps. Et 20 års materiale.

Surgery for herniated lumbar discs was performed on approximately 700 patients during the period 1963-83. 500 patients with a median observation of 13.5 years (5-25 years) were included in a follow-up study by reviewing journals and using a questionnaire. 35 of these patients (7%) had an acute operation. 398 patients (79.6%) were satisfied with the operation. There was a high positive correlation between the radiologic and peroperative findings and few complications after operation. 59 patients (11.8%) were reoperated and 94 patients (18.8%) were later hospitalized without operation because of lumbar pain. We conclude that patients who are to have surgery must be carefully selected, and that patients should be informed about the degenerative process, and the marked possibility of residual or repeated herniation and continuing lumbar pain.

[Morgagni Hernia]. / Hernia Morgagni.

The article describes a 65 year-old female with a 40 years' history of abdominal discomfort and a supposed intrathoracal lipoma who was admitted to hospital with acute obstruction of the large bowel. Emergency laparotomy revealed a subcostosternal diaphragmatic hernia (hernia of Morgagni) containing omentum and a segment of transverse colon.

[Inguinal actinomycoses]. / Aktinomykose i lysken.

The article describes a patient with the unusual inguinal location of actinomycosis. Actinomycosis is encountered relatively seldom in clinical practice, and differential diagnoses such as abscess/fistulas caused by other microorganisms, as well as neoplasms, should be considered.